Cyclic beta-ketoamide ACAT inhibitors

Abstract

Novel cyclic beta-ketoamides which contain an aryl moiety having utility as blood cholesterol lowering agents rendering them useful in the treatment of atherosclerosis.

I claim: 
     
       1. A compound of the formula wherein Y is oxygen or sulfur;   wherein Ar is selected from:   (a) phenyl which is unsubstituted or is substituted with from 1 to 3 substituents selected from: alkyl having from 1 to 6 carbon atoms and which is straight or branched,   alkoxy having from 1 to 6 carbon atoms and which is straight or branched,   phenoxy,   hydroxy,   fluorine,   chlorine,   bromine,   nitro,   trifluoromethyl,   --COOH,   --COOalkyl wherein alkyl has from 1 to 4 carbon atoms,   --NR 3  R 4  wherein R 3  and R 4  are independently hydrogen or alkyl of from 1 to 4 carbon atoms; wherein n is an integer of from 0 to 3;   wherein R 1  is selected from       (a) hydrogen;   (b) phenyl which is unsubstituted or is substituted with from 1 to 3 substituents selected from: alkyl having from 1 to 6 carbon atoms and which is straight or branched;   alkoxy having from 1 to 6 carbon atoms and which is straight or branched,   phenoxy,   hydroxy,   fluorine,   chlorine,   bromine,   nitro,   trifluoromethyl,   --COOH,   --COO alkyl wherein alkyl has from one to four carbon atoms,   --NR 3  R 4  wherein R 3  and R 4  have the meanings defined above; and     (c) the group ##STR13## wherein t is zero to 4; p is zero to 4 with the proviso that the sum of t and p is not greater than 5;   R 5  and R 6  are independently selected from hydrogen or alkyl having from 1 to 6 carbon atoms, or when R 5  is hydrogen, R 6  can be selected from the groups defined for R 7  and R 7  is phenyl or phenyl substituted with from 1 to 3 substituents selected from straight or branched alkyl having from 1 to 6 carbon atoms, straight or branched alkoxy having from 1 to 4 carbon atoms, straight or branched thioalkoxy having from 1 to 4 carbon atoms, phenoxy, hydroxy, fluorine, chlorine, bromine, nitro, trifluoromethyl, --COOH, --COO alkyl wherein alkyl has from one to four carbon atoms, or NR 3  R 4  wherein R 3  and R 4  have the meanings defined above; wherein R 2  is selected from ##STR14## wherein m is an integer from zero to three.     
     
     
       2. A compound of claim 1 wherein n is 1 to 3. 
     
     
       3. A compound of claim 2 wherein Y is oxygen. 
     
     
       4. A compound of claim 3 wherein Ar is phenyl substituted with alkyl having from 1 to 6 carbon atoms and is straight or branched. 
     
     
       5. A compound of claim 4 wherein phenyl is disubstituted in the 2 and 6 positions. 
     
     
       6. A compound of claim 5 which is N-[2,6-bis(1-methylethyl)phenyl]-2-oxo-3-phenyl-3-(2-pyridinyl)cyclopentanecarboxamide;   N-[2,6-bis(1-methylethyl)phenyl]-2-oxo-3-phenyl-3-(2-pyridinyl)cyclohexanecarboxamide;   N-[2,6-bis(1 methylethyl)phenyl]-2-oxo-3-phenyl-3-(2 pyridinylmethyl)cyclohexanecarboxamide.   
     
     
       7. A pharmaceutical composition which comprises a compound of claim 1 and a pharmaceutically acceptable carrier. 
     
     
       8. A method of lowering the cholesterol levels in a patient in need thereof which comprises administering to said patient an effective amount of a compound of claim 1.